PROJECT SUMMARY/ABSTRACT: Hypoxic-Ischemic brain Injury (HII) is a severe injury caused by oxygen deprivation to the brain at or near time of birth in preterm and/or low birth weight newborns. It is very important to recognize HII as soon as possible because early intervention improves outcomes. HII is one of the most common causes of mortality and morbidity in preterm neonates with an occurrence of ~60%. Preterm neonates experiencing HII are at risk for developing hypoxic-ischemic encephalopathy, cerebral palsy, periventricular leukomalacia, and hydrocephalus. The imaging-based diagnostic methods to identify HII are: Cranial ultrasonography has the benefit of being available at the baby?s bedside, but it has a low sensitivity for detecting the anomalies that are caused by HII due to its inability to measure tissue oxygen saturation, blind spots due to being out of probe range, and 2D images that lack spatial orientation to accurately locate ischemic areas. In contrast, second stage diagnostic tools, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET), have high sensitivity and specificity for the detection of brain injuries. However, they are not used as frontline modalities for routine screening of at-risk newborns, because MRI takes a long time (~1 hour), CT is using ionizing radiation, and PET requires a positron-emitting radionuclide. Small MRI units that have been installed and tested in a few neonatal ICUs are expensive and still require sedation during imaging. Near infrared spectroscopy (NIRS) has poor spatial resolution and poor penetration depth. All of these modalities require transporting clinically unstable newborns out of the Neonatal Intensive Care Unit, often require sedation that is associated with risks (i.e. hypotension, hemodynamic changes, or allergic reaction), and have a relatively high cost. We have been developing a novel point-of-care 3D neonatal PhotoAcoustic Tomography (3D-nPAT) instrument to improve the detection and measurement of hypoxic-ischemic brain injury in neonates without the need for sedation, radiation or radionuclides. 3D-nPAT can be used to determine the location and extent of brain injury, allowing for earlier treatment which may circumvent a variety of neural complications, and improve the functional outcome from cerebral injuries. The long-term goal of this research project is to provide a fast, portable, point-of-care diagnostic imaging method for neonates suspected of hypoxic-ischemic brain injury. Our central premise is that the high sensitivity of PAI to oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) (well documented in both animal models and humans), in addition to the very thin skull (~ 2mm) in preterm and/or low birth weight neonates, provides an opportunity to use photoacoustic technology to design the non-invasive 3D-nPAT. The immediate objective of this proposal is to optimize the current 3D-nPAT system, assess the feasibility of it to detect hypoxic-ischemic brain injury in a canine model, and evaluate it on 10 patients in a clinical study. The proposed 3D-nPAT instrument, will provide neonatologists with an affordable, fast, portable, non-invasive, vascular functional imaging tool to map hypoxic-ischemic injuries to the neonatal brain that currently require the use of multiple specialized systems.